Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was conducted to examine an involvement of G protein in the action of activin A in rat parenchymal liver cells. Activin A induced a dose-dependent increase in inositol phosphates in cells prelabelled with [3H]inositol. The effect of activin A was completely blocked by pretreatment of the cells with pertussis toxin. In contrast, pertussis toxin had little effect on angiotensin II-induced production of inositol phosphates. Both activin A and angiotensin II inhibited glucagon-mediated production of cAMP. Pretreatment of the cells with pertussis toxin blocked the inhibition induced by both activin A and angiotensin II. In permeabilized cells, activin A augmented production of inositol phosphates. Activin-mediated production of inositol trisphosphate was enhanced by GTP-gamma S and was attenuated by GDP-beta S. These results suggest that a pertussis toxin-sensitive G protein(s) may be involved in the action of activin A in hepatocytes.
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PMID:Pertussis toxin blocks activin A-induced production of inositol phosphates in rat hepatocytes. 132 3

The effect of activin-A on glycogenolysis was studied in isolated rat hepatocytes. Activin-A stimulated glucose output in hepatocytes in a dose-dependent manner. The maximal effect of the glycogenolytic action of activin-A, which was about 50% of the glucagon action, was obtained at 10(-9) M. When 10(-9) M activin-A and 5 x 10(-9) M glucagon were added simultaneously, the actions of these two agents were additive. In contrast, there was no additivity when 10(-9) M activin-A and 10(-8) M angiotensin-II were added. Activin-A did not increase cAMP at any doses tested, but induced a rapid increase in cytoplasmic free calcium concentration. Activin-A increased the cytoplasmic free calcium concentration even in the presence of 1 microM extracellular calcium, suggesting that activin-A caused calcium release from an intracellular calcium pool(s). The internal calcium pool affected by activin-A appeared to be the same as that affected by either angiotensin-II or vasopressin. When [3H] inositol-labeled hepatocytes were incubated with activin-A, radioactivity in the inositol trisphosphate fraction was rapidly increased. These results indicate that activin-A acts on rat hepatocytes and stimulates glycogenolysis by activating the calcium messenger system.
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PMID:Stimulation of glucose production by activin-A in isolated rat hepatocytes. 254 39

Expression of activin A in fetal rat pancreas was studied immunohistochemically by using anti-activin A antibody. On embryonic day 12 (E12), cells in cap-like pancreatic anlage were stained with anti-activin A antibody. In these sections, no immunoreactive insulin or glucagon was observed. On E13.5, cells containing immunoreactive activin A were observed in pancreatic anlage. These cells were also stained by both anti-glucagon and anti-insulin antibodies. On E15, a cluster of cells could be recognized as a primitive islet. In the primitive islet, cells containing immunoreactive activin A were observed. Activin-positive cells were located mainly in the mantle of the primitive islet but some were located in the core of the primitive islet. These activin-positive cells also expressed glucagon. Among them, cells also containing insulin were observed. In addition to activin-positive cells, cells containing only insulin were detected in the core of the primitive islet. These results indicate that immunoreactive activin A is expressed in fetal pancreas. The expression of activin A is an early event during the development of pancreatic endocrine cells.
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PMID:Expression of immunoreactive activin A in fetal rat pancreas. 759

Activin-A, a member of the transforming growth factor-beta supergene family, stimulates insulin secretion in rat pancreatic islets and causes glycogenolysis in isolated rat hepatocytes. These observations prompted us to determine whether activin-A existed in rat pancreas by using an immunocytochemical method. Cells in pancreatic islets were stained by antibody against activin-A, whereas no immunoreactivity was observed in exocrine pancreas. Cells localized in the mantle of the islets were densely stained by the antibody. Immunoelectron microscopic study showed that activin-A existed in secretory granules in both A- and D-cells. Furthermore, studies using a double labeling method revealed that activin-A coexisted with glucagon in secretory granules in A-cells and with somatostatin in D-cells. Antibody against inhibin-A weakly stained cells in both the core and mantle of the islets only when the rat was pretreated with colchicine. Subtypes of activin subunit in islets were identified to be beta A by a reverse transcription-polymerase chain reaction method. In addition, mRNA for inhibin alpha-subunit was expressed in islets. However, mRNA for these inhibin subunits was not detected in exocrine pancreas. To further examine the action of activin-A on insulin secretion, we examined the effect of activin-A in a flow-through perifusion system. Activin-A induced a biphasic insulin secretory response in the presence of 2.8 mM glucose, and a low concentration of activin-A, which does not stimulate insulin secretion by itself, markedly enhanced glucose-mediated insulin secretion at concentrations above 2.8 mM glucose. Inhibin-A did not affect insulin secretion. These results suggest the existence of activin-A in A- and D-cells of rat pancreatic islets and raise the possibility that activin-A acts as a physiological regulator of carbohydrate metabolism.
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PMID:Existence of activin-A in A- and D-cells of rat pancreatic islet. 834 2

Activin A now used as a recombinant product was first isolated from ovarian fluid. Its effects on insulin and glucagon secretion, 45Ca2+ net uptake, 86Rb+ efflux and inositol-trisphosphate (Ins-1,4,5-P3) content were investigated in rat pancreatic islets. Activin A increased insulin secretion at either 3.0, 8.3 or 16.7 mM glucose. It decreased glucagon secretion at 3.0, had no effect at 8.3 and increased glucagon secretion at 16.7 mM glucose. The effect on insulin release was concentration dependent; effects were obvious at 1 and 10 nM activin A. The effect on insulin release was paralleled by an effect on 45Ca2+ net uptake. 10 nM activin A were effective in elevating Ins-1,4,5-P3 content at either glucose concentration used. 86Rb+ efflux as an indicator for closing K+ channels which leads to a depolarization of the beta-cell membrane and which is a prerequisite for Ca++ influx was inhibited by activin A at a low glucose concentration (3.0 mM). The data indicate that the new peptide activin A elevates insulin release at various glucose concentrations: at low and high glucose concentrations 45Ca2+ uptake is involved. At low glucose concentrations inhibition of 86Rb+ efflux is a prerequisite sufficient to lead to a depolarization and subsequent Ca++ uptake; accumulation of Ins-1,4,5-P3 probably helps mediating the insulinotropic effect by additionally elevating intracellular Ca++.
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PMID:Activin A: its effects on rat pancreatic islets and the mechanism of action involved. 836 69

Rat pancreatic AR42J cells possess exocrine and neuroendocrine properties. Activin A induces morphological changes and converts them into neuron-like cells. In activin-treated cells, mRNA for pancreatic polypeptide (PP) but not that for either insulin or glucagon was detected by reverse transcription-PCR. About 25% of the cells were stained by anti-PP antibody. When AR42J cells were incubated with betacellulin, a small portion of the cells were stained positively with antiinsulin and anti-PP antibodies. The effect of betacellulin was dose dependent, being maximal at 2 nM. Approximately 4% of the cells became insulin positive at this concentration, and mRNAs for insulin and PP were detected. When AR42J cells were incubated with a combination of betacellulin and activin A, approximately 10% of the cells became insulin positive. Morphologically, the insulin-positive cells were composed of two types of cells: neuron-like and round-shaped cells. Immunoreactive PP was found in the latter type of cells. The mRNAs for insulin, PP, glucose transporter 2, and glucokinase, but not glucagon, were detected. Depolarizing concentration of potassium, tolbutamide, carbachol, and glucagon-like peptide-1 stimulated the release of immunoreactive insulin. These results indicate that betacellulin and activin A convert amylase-secreting AR42J cells into cells secreting insulin. AR42J cells provide a model system to study the formation of pancreatic endocrine cells.
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PMID:Betacellulin and activin A coordinately convert amylase-secreting pancreatic AR42J cells into insulin-secreting cells. 860 30

Activin A is a multifunctional protein known to stimulate insulin secretion (Yasuda H et al., (1993) Endocrinology 133, 624-630). The present study was conducted to determine whether activin A augments insulin secretion in the absence of ambient glucose. In the presence of 2.7 mM glucose, and 1.25 mM calcium, activin A induced a biphasic secretory response of insulin. In the absence of glucose in perifusate, activin A induced a small but significant release of insulin. The effect of activin A was monophasic in the absence of glucose. In contrast, glucagon-like peptide-1 (GLP-1) had no effect on insulin secretion under the same conditions. However, GLP-1 could enhance insulin secretion induced by activin A in glucose-free medium. Activin A induced a transient increase in cytoplasmic-free calcium concentration, [Ca2+]c, in a fura-2-loaded islet superfused with glucose-free buffer. Again, GLP-1 was without effect on [Ca2+]c by itself in glucose-free buffer. In the presence of activin A, however, GLP-1 could induce an elevation of [Ca2+]c. Finally, GLP-1, but not activin A, increased cAMP content in islets incubated in glucose-free medium. These results indicate that activin A, but not GLP-1, induces insulin secretion in glucose-free medium. Activin A is able to reproduce partly the effect of glucose to support the action of GLP-1 in glucose-free medium.
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PMID:Initiation of insulin secretion in glucose-free medium by activin A. 867 16

To elucidate the regulation of follistatin production in the liver, we studied changes in steady-state follistatin mRNA levels in cultured rat hepatocytes. Activin A stimulated follistatin mRNA levels in a time- and concentration-dependent manner. The stimulatory effect of activin A on follistatin mRNA was significant at 2 h, maximal at 6 h and declined thereafter. Incubating the cells with EGF increased follistatin mRNA levels at 48 h and later. The EGF-induced increase in follistatin mRNA was markedly inhibited by exogenous follistatin in the culture medium, which blocks the action of activin A synthesized in hepatocytes, suggesting that endogenous activin A at least partly mediated the effect of EGF. We also examined the effects of transforming growth factor-beta (TGF-beta), glucagon and alpha-adrenergic agonist, phenylephrine, on follistatin mRNA levels. TGF-beta increased the follistatin mRNA to levels similar to those caused by activin A. Phenylephrine and glucagon also increased follistatin mRNA levels but the effects were transient and weaker than those caused by activin A. Finally, follistatin mRNA levels were markedly increased in remnant liver 3 h after 70% hepatectomy. The mRNA remained elevated for up to 72 h. These results indicate that the expression of mRNA for follistatin is positively controlled by activin A, TGF-beta and other hormones or neurotransmitters. The stimulatory effect of EGF on follistatin mRNA is mediated by activin A released from hepatocytes.
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PMID:Regulation of the expression of follistatin in rat hepatocytes. 942 29

Activin A is expressed in endocrine precursor cells of the fetal pancreatic anlage. To determine the physiological significance of activins in the pancreas, a transgenic mouse line expressing the truncated type II activin receptor under the control of beta-actin promoter was developed. Histological analyses of the pancreas revealed that the pancreatic islets of the transgenic mouse were small in size and were located mainly along the pancreatic ducts. Immunoreactive insulin was detected in islets, some acinar cells, and in some epithelial cells in the duct. In addition, there were abnormal endocrine cells outside the islets. The shape and the size of the endocrine cells varied and some of them were larger than islets. These cells expressed immunoreactive insulin and glucagon. In the exocrine portion, there were morphologically abnormal exocrine cells, which did not form a typical acinar structure. The cells lacked spatial polarity characteristics of acinar cells but expressed immunoreactive amylase, which was distributed diffusely in the cytoplasm. Plasma glucose concentration was normal in the transgenic mouse before and after the administration of glucose. The insulin content of the pancreas in transgenic and normal mice was nearly identical. These results suggest that activins or related ligands regulate the differentiation of the pancreatic endocrine and exocrine cells.
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PMID:Impaired differentiation of endocrine and exocrine cells of the pancreas in transgenic mouse expressing the truncated type II activin receptor. 1023 50

Activin, a member of the transforming growth factor-beta superfamily, has been shown to be a critical regulator in exocrine and endocrine pancreas formation. The purpose of our study was to describe the ontogeny of activin B and its inhibitor, follistatin, in developing pancreas and to elucidate potential mechanisms for exocrine and endocrine lineage selection. Mouse embryonic pancreata were dissected at various ages (day 10 [E10.5] to birth [E18.5]), sectioned, and immunostained for activin B (one of two existing isomers, A and B), follistatin, insulin, and glucagon. In addition, reverse transcriptase-polymerase chain reaction was employed to determine the messenger RNA expression of follistatin in isolated pancreatic epithelia and mesenchyme of various ages. Activin B was first detected at E12.5 in epithelial cells coexpressing glucagon. At E16.5 these coexpressors appeared as clusters in close proximity to early ducts. By E18.5 activin B was localized to forming islets where cells coexpressed glucagon and were arranged in the mantle formation characteristic of mature alpha cells. Follistatin was found to be ubiquitous in pancreatic mesenchyme at early ages by immunohistochemical analysis, disappearing sometime after E12.5. Follistatin reappeared in E18.5 islets and remains expressed in adult islets. Follistatin messenger RNA was first detected in epithelium at E11.5, preceding its protein expression in islets later in gestation. We propose that mesenchyme-derived follistatin inhibits epithelium-derived activin at early embryonic ages allowing for unopposed exocrine differentiation and relative suppression of endocrine differentiation. At later ages the decrease in the amount of mesenchyme relative to epithelium and the subsequent drop in follistatin levels liberates epithelial activin to allow differentiation of endocrine cells to form mature islets by the time of birth.
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PMID:Ontogeny of activin B and follistatin in developing embryonic mouse pancreas: implications for lineage selection. 1076 89


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